Research will continue on the development of somatostatin analogs with increased activities and selectivity for inhibition of glucagon, growth hormone, and gastric acid secretion. These compounds could have therapeutic value in the treatment of diabetes mellitus, acromegaly, gastric ulcers, acute pancreatitis, and possibly certain hormone-dependent tumors. An additional aspect of this work, which has assumed much greater importance with our recent discovery of the first peptice antagonist of somatostatin, is the investigation of the structural features responsible for antagonist activity. The availability of an antagonist will help to elucidate the functions of somatostatin in controlling many physiological processes. It is also possible that selective antagonists can be developed which could act as specific pseudo-releasing factors for several important hormones. Synthesis of analogs will continue to be by established solid-phase methods, except for the new short, cyclic antagonist peptides where new synthetic routes have been established. Both agonists and antagonists will be tested in vivo in the rat for their inhibitory of stimulatory effects on Nembutal-stimulated growth hormone release and insulin and glucagon levels present in hepatic portal blood samples. These three hormones are measured by standard radioimmunoassay techniques. A colaborative arrangement has been made for examining analog effects on gastrin-stimulated gastric acid release in the cat.